Thin surface coatings on implantable medical articles have proved to be valuable in cases where it is desired to provide the article surface with a property that is not present on the uncoated surface. Polymeric coatings have been used to improve the wettability and lubricity of surfaces, and have also been used to present or elute drugs. For example, drugs presented on, or delivered from, the article surface can locally or systemically affect blood and vascular components thereby affecting bodily processes such as hemostasis and angiogenesis.
It has become appreciated that function of the implanted device at the site of implantation can be greatly enhanced by improving its compatibility in the context of the tissue response that occurs as a result of the implantation. Ideally, improved compatibility would allow surfaces of the implanted device to mimic natural tissue exposed by an injury and provide an environment for the formation of normal tissue as a result of the healing process. Polymeric coatings have been applied to surfaces of implantable devices in attempts to promote such tissue formation following implantation. Such surfaces would ideally attract components such as cells to the surface of the device and also promote proliferation of the cells for the formation of tissue.
Some polymeric coatings have been prepared using extracellular matrix proteins such as collagen as a coating material in attempts to attract cells to promote tissue growth on the coated surface. In the body, collagens have been shown to interact with various proteins including von Willebrand factor (VWF), integrins, and bone growth proteins. The direct or indirect result of these interactions can affect cell attachment and tissue formation. However, the process of mimicking the natural function of collagen on a synthetic surface is technically challenging. Preparation of collagen-containing coatings can often result in surfaces that do not provide the intended function following implantation. In coatings wherein collagen is not properly immobilized, collagen can leach out or be released from the surface, rendering the surface ineffective. Also, some chemistries for covalent immobilization of collagen may reduce or destroy collagen activity, such as by altering peptide motifs that are important for the interaction of collagen with other biological components. Certain chemistries may also alter the macromolecular configuration of collagen so that it does not resemble natural collagen. Further, even if collagen is successfully immobilized in a coating, the coating may have the ability to attract cells to a certain extent, but not in a manner that provides for subsequent proliferation of the cells, which is important for tissue formation.
The investigators have discovered that there is a need to prepare coatings that promote enhanced cell attachment and proliferation of cells on the coated surface, particularly of endothelial cells and fibroblasts and have discovered novel and inventive coatings that achieve these results. These cell types are useful for enhancing tissue growth around an implant.